Depo-provera

Depo-Provera is a systemic contraceptive drug of hormonal type. It belongs to the category of gestagens.

Indications Depo-checks

The drug is used as a method of long-term contraception. As a short-term contraceptive, the drug can be used in the following situations:

• partners of men who have had a vasectomy – as a means of protection until the vasectomy becomes effective;
• women who have been immunized against the rubella virus - to prevent the possibility of pregnancy during the period of activity of this pathology;
• women awaiting sterilization procedures.

Teenagers aged 12-18 years.

The drug is prohibited for use before the onset of menstruation. It is prescribed to children only in cases where other contraceptive methods have proven unacceptable or ineffective.

Release form

Released as an injection suspension in vials or ready-to-use syringes with a volume of 1 ml. Inside a separate package - 1 such syringe or vial.

Pharmacodynamics

Medroxyprogesterone acetate has antiandrogenic, antiestrogenic and antigonadal properties.

Tests comparing changes in bone mineral density in people who used the drug and those who received intramuscular injections of the drug (150 mg) did not reveal significant differences in bone mineral density loss between the two groups after 2 years of treatment.

In the second controlled drug trial in adult women, 150 mg injections were used (treatment period was up to 5 years). An average decrease in bone density in the femur and spine was observed (by about 5-6% compared to no noticeable changes in these values in the control group). The decrease in bone density was more pronounced during the first 2 years of drug use and decreased in subsequent years. The average changes in lumbar density were -2.86% (year 1), -4.11% (year 2), -4.89% (year 3), -4.93% (year 4), and -5.38% (year 5). The average decreases in femur and neck density were similar to the above values.

After the drug was discontinued, the density indices increased compared to the initial figures observed during the post-therapeutic period. With longer therapy, a decrease in the rate of restoration of density indices was usually observed.

Changes in density indicators in girls aged 12-18 years.

Data from an open, non-randomized drug trial of the drug (150 mg at 12-week intervals between treatments) for 240 weeks (or 4.6 years) with subsequent post-therapeutic monitoring of parameters in girls aged 12-18 years also revealed that intramuscular injections of the drug resulted in a significant decrease in bone mineral density (compared to baseline values). In girls who received ≥4 injections over a 60-week period, the average decrease in density in the lumbar region was -2.1% (use for 240 weeks; 4.6 years). For the femur and its neck, the average decreases in density were -6.4% and -5.4%, respectively.

The post-treatment examinations showed (based on average values) that the lumbar density level returned to its initial values 1 year after the end of treatment, and the density in the thigh area was completely restored after 3 years. However, it is important to note that many patients refused to participate in further testing before its completion. As a result, the test data are based on a small number of treated girls (71 people after 60 weeks after the end of the course, and only 25 after 240 weeks).

In a disparate group of patients who did not undergo the above-described therapy and had different bone mass values at baseline (compared to the girls who used Depo-Provera), an increase in the average density level was observed after 240 weeks – 6.4% (lower back), 1.7% (femur) and 1.9% (femoral neck).

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Pharmacokinetics

The active component of the drug, administered parenterally, is a progestational steroid with a prolonged effect. A long duration of action is ensured by the slow process of absorption of the substance from the injection site. After the administration of 150 mg/ml of the drug, its plasma indicator was 1.7±0.3 nmol/l. After 2 weeks, these indicators were 6.8±0.8 nmol/l. The initial values of the drug concentration were observed at the end of 12 weeks after the procedure. At small dosages, the plasma indicators of medroxyprogesterone acetate are considered to be directly dependent on the doses of the drug used. No accumulation of the substance in the serum is observed.

The active component of the drug is excreted with feces or urine. The plasma half-life is approximately 6 weeks (after a single injection). There is evidence of at least 11 decay products. All elements are excreted with urine, and some of them are excreted in the form of conjugates.

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Dosing and administration

Before performing an injection, it is necessary to make sure that the dose of suspension used has a completely uniform consistency. To do this, shake the bottle with the medicine thoroughly before the procedure.

The drug is administered intramuscularly, deeply. It is necessary to make sure that the injection is performed precisely in the area of muscle tissue (it is recommended to use the gluteal muscle, although options with other muscles are also possible - for example, the deltoid).

Before the procedure, the injection site is cleaned using standard techniques.

The 1st injection is 150 mg of the drug. To ensure proper contraceptive effect during the 1st cycle of use, the intramuscular injection is administered during the first 5 days of the standard menstrual cycle. If the procedure is performed in accordance with these instructions, no additional contraceptive measures will be required.

In the postpartum period: to increase confidence that the patient is not pregnant at the time of the first injection, the procedure must be performed within 5 days after childbirth (with the adjustment that the mother is not breastfeeding the child).

There is information that shows that women who start using Depo-Provera immediately after childbirth may experience severe, prolonged bleeding. As a result, the drug should be used with caution during this period of time. Patients who decide to use the drug immediately after childbirth or after an abortion should be informed of the possible risks of such a decision. In addition, it should be noted that in non-breastfeeding mothers, ovulation may occur as early as the 4th week after the birth process.

Nursing mothers can have the first injection at least 6 weeks after the baby is born – during this period the baby’s enzymatic system is more fully developed. Further procedures are performed at intervals of 12 weeks.

Subsequent doses: the drug should be administered at 12-week intervals, but if injections are given no more than 5 days after the specified time, additional contraceptive measures (for example, barrier methods) are not required.

Partners of men who have had a vasectomy may require a second intramuscular injection of the drug (150 mg) 12 weeks after the first. This is required by a small number of women - those whose partners' sperm counts have not dropped to zero.

If, for any reason, the interval since the previous procedure exceeds 89 days (12 weeks + 5 days), pregnancy must first be ruled out before the next administration of the drug. The woman will then need to use additional contraceptive methods (barrier) for 14 days from the moment the new dose of the drug is administered.

When switching from other contraceptive drugs.

The drug is used in such a way that the contraceptive effect is continuous. Therefore, it is necessary to take into account the mechanisms of action of other drugs (for example, women switching from oral contraception need to enter the 1st dose of Depo-Provera within 7 days from the moment of taking the last tablet).

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Use Depo-checks during pregnancy

Depo-Provera should not be administered to pregnant women for either therapy or diagnostic procedures.

The doctor is required to examine the patient for pregnancy before administering the first injection of the drug.

The active component of the drug with its decay products can penetrate into the mother's milk, but there is no information that allows us to consider this dangerous for the baby. Children who were exposed to the drug during the lactation period were examined regarding its impact on their behavior and development before the onset of puberty. No negative effects were noted.

Contraindications

Main contraindications:

• the presence of intolerance to the active component of the drug and its auxiliary elements;
• use as a means of contraception in the case of a patient with diagnosed or suspected hormone-dependent malignant tumors in the genital area or mammary gland;
• in the presence of severe liver pathologies (or if they are present in the anamnesis, when the functional values of the liver have not returned to normal);
• appointment for monotherapy or for complex treatment together with estrogens for women/girls who have pathological uterine bleeding (until the diagnosis is established and the possibility of the presence of malignant tumors in the genital area is excluded);
• use in elderly patients.

Side effects Depo-checks

Using Depo-Provera may cause the following side effects:

• reactions of the auditory organs together with the vestibular apparatus: vertigo occasionally develops;
• Gastrointestinal manifestations: abdominal discomfort or pain often occurs. Nausea or flatulence often occurs. Gastrointestinal disorders are occasionally observed. Rectal bleeding is observed sporadically;
• infectious or invasive processes: vaginitis often appears;
• Metabolic and alimentary disorders: often there is a deterioration or increase in appetite. Less often, there is a decrease/increase in weight, as well as fluid retention;
• disorders of the musculoskeletal system and connective tissues: often there is pain in the back. Sometimes there are muscle spasms, arthralgia, and pain in the limbs. Osteoporosis may develop (this includes osteoporotic fractures), swelling in the armpits, and a decrease in the density of bone tissues inside;
• manifestations from the nervous system: headaches are often observed. Dizziness occurs less often. Sometimes migraines, a feeling of drowsiness and convulsions appear. Paralysis is occasionally observed. Fainting may develop;
• Reactions of the reproductive organs and mammary glands: often observed pain in the sternum, amenorrhea, bleeding between periods, as well as leukorrhea, painful sensations in the pelvic area and metrorrhagia with hypermenorrhea. Less common are vaginal discharge, dryness of the vaginal mucosa, infections in the urogenital tract, changes in the size of the mammary glands, dysmenorrhea and dyspareunia, as well as uterine hyperplasia, PMS and ovarian cysts. Rarely, bleeding from the nipples and seals in the mammary glands appear. The development of galactorrhea, pathological uterine bleeding (increased, weakened or irregular), obstruction of the lactation process, the appearance of a cyst in the vagina or signs similar to pregnancy, as well as the inability to restore reproductive activity are possible. There is a possibility of erosion of the cervix and the development of prolonged anovulation;
• vascular disorders: hot flashes often occur. Varicose veins, increased blood pressure, pulmonary embolism and thrombophlebitis are occasionally observed. DVT and thromboembolic disorders may develop;
• disorders of cardiovascular function: tachycardia occasionally occurs;
• immune manifestations: sometimes hypersensitivity reactions occur (for example, anaphylactoid symptoms and anaphylaxis, as well as Quincke's edema);
• reactions of the hepatobiliary system: sometimes pathological liver enzyme levels or jaundice are observed. Functional liver disorder is possible;
• manifestations from the subcutaneous layer and dermatological diseases: rashes often occur, as well as alopecia and acne. Sometimes dermatitis, swelling, urticaria and itching occur, as well as hirsutism, chloasma and ecchymosis. Scleroderma and stretch marks on the skin may appear;
• Injection site manifestations and systemic disorders: reactions at the injection site (including abscess and pain) as well as paresthesia, increased fatigue and asthenia often occur. Fever or chest pain sometimes develops. Dysphonia, thirst and paralysis rarely occur. Facial nerve paralysis is possible;
• laboratory test data: sometimes abnormalities are observed in smears taken from the cervix. Glucose tolerance is occasionally reduced;
• Mental disorders: often there is a feeling of nervousness, irritability or emotional disturbance and changes in mood, as well as depression, insomnia, anorgasmia and decreased libido. Sometimes there is a feeling of anxiety;
• tumors of a malignant, benign or non-specific type (this includes polyps with cysts): breast cancer occasionally develops;
• diseases of the lymph and systemic blood flow: anemia is occasionally observed. Development of blood dyscrasia is possible;
• reactions of the respiratory organs and mediastinum with the sternum: dyspnea is sometimes noted.

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Interactions with other drugs

When combined with aminoglutethimide, significant inhibition of the bioavailability of the drug Depo-Provera is possible.

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Storage conditions

The suspension must be kept out of reach of children. Freezing is prohibited. Temperature values are maximum 25°C.

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Shelf life

Depo-Provera can be used for a period of 5 years from the date of manufacture of the drug.